An aminopeptidase N-activatable chemiluminescence probe for image-guided surgery and metastasis tracking of tumor

Malignant tumors are a severe threat to human health. Surgical removal is still the preferred method in clinical practice among the many treatment strategies. Nevertheless, tiny residual tumor lesions and distant metastases are always missed during surgery, resulting in tumor recurrence. Therefore, it is important for doctors to distinguish residual tumor tissues and distant metastases from normal tissues but remains challenging. Herein, we rationally designed an aminopeptidase-activatable chemiluminescence (CL) probe Ala-PD to distinguish cancer tissues from normal tissues through a spraying manner. In vitro studies revealed that Ala-PD could specifically respond to APN with a ∼26-fold CL signal turn-on ratio and a limit of detection of 0.531 ng/mL. Moreover, Ala-PD exhibited an ultrahigh tumor-to-normal tissue CL ratio of above 1.2 × 106. Furthermore, the ability of Ala-PD to image metastatic tumor tissues was also achieved in tumor-bearing mouse, highlighting the potential of Ala-PD to be applied in image-guided surgery clinically.